PROJECT SUMMARY/ABSTRACT We request funds for the purchase of an FEI Talos L120C Transmission Electron Microscope (TEM) for the examination of biological samples at cryo and room temperatures. The new instrument will help provide for the electron microscopy needs of over 60 NIH-funded laboratories at the University of Massachusetts Medical School (UMMS) and UMMS Graduate School of Biomedical Sciences (GSBS). It will be housed in the Core Electron Microscopy Facility of the Medical School, and will replace a 30+ year old Philips CM10, that while still functioning, is now considered obsolete and is becoming unreliable, and is no longer supported by the manufacturer (parts or service). The Core Electron Microscopy facility supports projects ranging from routine studies of thin sections of cells and tissues, the macromolecular structure of muscle, microtubule formation and stabilization, stem cell and germ cell differentiation, cilia and flagella structure, to cryo-EM studies of liposomes, AAV vectors, exosomes, as well as single particle observation and reconstructions required for understanding the detailed structural changes associated with human disease. All are important topics in the understanding of the normal function and structure of the human body and all require transmission electron microscopy. The Talos L120C offers a wide range of outstanding features and benefits over our obsolete Philips CM10. These include not only its modern, efficient, user-friendly design, but also the cryo-capabilities that the CM10 lacks. This last feature will be used for studies of liposomes and exosomes structure and for screening cryo-grids prior to imaging on the direct detector instruments available in the new high-end cryo facility at UMMS. All users, from beginning students to our most skilled microscopists, will benefit from this cutting-edge instrument. Funding this grant will update our facility with a modern instrument that will support more than 100 researchers and graduate students at UMMS as well as several colleges in the surrounding area. The new instrument will greatly enhance the ability of our investigators and students to carry out their electron microscopy-related studies, it will greatly improve the quality and speed of data collection, and it will make possible types of observations that are impossible with our older (obsolete) instrument.